The Small GTPase ARF6 Activates PI3K in Melanoma to Induce a Prometastatic State.

ABSTRACT: Melanoma has an unusual capacity to spread in early-stage disease, prompting aggressive clinical intervention in very thin primary tumors. Despite these proactive efforts, patients with low-risk, low-stage disease can still develop metastasis, indicating the presence of permissive cues for distant spread. Here, we show that constitutive activation of the small GTPase ARF6 (ARF6^Q67L) is sufficient to accelerate metastasis in mice with BRAF^V600E/Cdkn2a^NULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. ARF6^Q67L promoted spontaneous metastasis from significantly smaller primary tumors than PTEN^NULL, implying an enhanced ability of ARF6-GTP to drive distant sprea

SUBMITTER: Yoo JH 

PROVIDER: S-EPMC7197377 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature